Dietary Sutherlandia and Elderberry Mitigate Cerebral Ischemia-Induced Neuronal Damage and Attenuate p47phox and Phospho-ERK1/2 Expression in Microglial Cells

Abstract

Sutherlandia (Sutherlandia frutescens) and elderberry (Sambucus spp.) are used to promote health and for treatment of a number of ailments. Although studies with cultured cells have demonstrated antioxidative and anti-inflammatory properties of these botanicals, little is known about their ability to mitigate brain injury. In this study, C57BL/6 J male mice were fed AIN93G diets without or with Sutherlandia or American elderberry for 2 months prior to a 30-min global cerebral ischemia induced by occlusion of the bilateral common carotid arteries (BCCAs), followed by reperfusion for 3 days. Accelerating rotarod assessment at 24 h after BCCA occlusion showed amelioration of sensorimotor impairment in the mice fed the supplemented diets as compared with the ischemic mice fed the control diet. Quantitative digital pathology assessment of brain slides stained with cresyl violet at 3 days after ischemia/reperfusion (I/R) revealed significant reduction in neuronal cell death in both dietary groups. Immunohistochemical staining for ionized calcium-binding adapter molecule-1 demonstrated pronounced activation of microglia in the hippocampus and striatum in the ischemic brains 3 days after I/R, and microglial activation was significantly reduced in animals fed supplemented diets. Mitigation of microglial activation by the supplements was further supported by the decrease in expression of p47phox, a cytosolic subunit of NADPH oxidase, and phospho-ERK1/2, a mitogen-activated protein kinase known to mediate a number of cytoplasmic processes including oxidative stress and neuroinflammatory responses. These results demonstrate neuroprotective effect of Sutherlandia and American elderberry botanicals against oxidative and inflammatory responses to cerebral I/R.

Effects of Vitamin D3 on the NADPH Oxidase and Matrix Metalloproteinase 9 in an Animal Model of Global Cerebral Ischemia

“…The authors have suggested that NOX activation arose in medium spiny neurons and endothelial cells at the early phase and in reactive microglia at the late phase. Additionally, increased p47 phox immunoreactivity was demonstrated in the hippocampus and striatum of the same mice strain 72 hours after 30 minutes of global cerebral ischemia [ 57 ]. Supplementation with vitamin D3 prior to ischemia, in our study, was followed by reduced expression of gp91 phox and p47 phox subunits in both the cortex and hippocampus, increased expression of p22 phox in the cortex and decreased expression of this subunit in the hippocampus, and increased expression of p67 phox in the hippocampus.…”

Phytochemicals and botanical extracts regulate NF-κB and Nrf2/ARE reporter activities in DI TNC1 astrocytes

“…Similar anti-inflammatory activity was reported in murine macrophages, but did not appear to be mediated by sutherlandiosides or sutherlandins, which are glycosylated derivatives (Lei et al, 2015a). Moreover, our recent in vivo studies demonstrated that dietary Sutherlandia mitigates cerebral ischemia-induced neuronal damage, in part by attenuating p47phox and phospho-ERK1/2 expression in microglial cells(Chuang et al, 2014). The present study showed that Sutherlandia extracts not only inhibit LPS-induced NF-κB activity (Fig.…”

Medicinal Attributes of American Elderberry

“…However, promising preclinical research exists. Mice fed diets containing American elderberry suffered substantially less disability after 24 h and less neuronal cell death after 3 days in response to global cerebral ischemia (effectively, an induced stroke) than non-supplemented mice (Chuang et al 2014 ). Flowers of Sambucus cerulea , which was once treated as a subspecies of S. nigra though it is morphologically distinct (Applequist 2015 ), are used by members of the North American Lumbee tribe to alleviate symptoms of Parkinson’s disease, and in vitro the extract has neuroprotective activities, including improvement of mitochondrial function in neurons and protection against rotenone neurotoxicity (de Rus Jacquet et al 2017 ).…”